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https://doi.org/10.5272/jimab.2019253.2692 Journal of IMAB Journal of IMAB - Annual Proceeding (Scientific Papers). 2019 Jul-Sep;25(3) ISSN: 1312-773X https://www.journal-imab-bg.org Original article

GLUTEN-SENSITIVE ENTEROPATHY – A POTENTIALLY CURABLE CAUSE OF HEPATIC DISORDERS

Lili Grudeva Clinic of , and Nutrition, Department of Internal , Medical University of Varna, Bulgaria.

ABSTRACT when hypertransaminasemia is observed without the pres- Introduction: The clinical spectrum of -sen- ence of other causes of liver dysfunction. sitive enteropathy is remarkably varied and the can affect many extraintestinal organs and systems, in- Keywords: gluten-sensitive enteropathy (GE), cluding the liver. Liver involvement, which is observed hypertransaminasemia, gluten-free diet (GFD) in patients with gluten-sensitive enteropathy, varies from an asymptomatic increase of hepatic enzymes or non-spe- INTRODUCTION cific reactive (cryptogenic hepatic disorders) to Gluten-sensitive enteropathy (GE) is an chronic . The histological changes and the autoimmune disease of the digestive system in which an dynamics of enzymes are notably different after a gluten- abnormal reaction to gluten [1] is developed – the pro- free diet (GFD) treatment. tein fraction in wheat, rye, barley, and to a lesser degree Patients and Methods: A clinical observation in- – in oats. The condition is one of the most widely spread cluded 112 patients with gluten-sensitive enteropathy and gastrointestinal disorders with a large spectrum of clini- 22 patients with gluten sensitivity, who passed through cal manifestations [2]. the Clinic of Gastroenterology, Hepatology and Nutrition The exact cause of the liver damage in patients at St. Marina University Hospital, Varna for the period from with GE has not been studied well yet [3]. January, 2005 to June, 2015. Thirty-four men and 78 However, it is known that hypertransaminasemia women between the ages of 18 and 76 were included. The can be an initial manifestation of GE [4]. There are nu- control group consisted of 22 patients of whom 6 were merous hepatic diseases, which can be related to it [5]. men and 16 – women. Results and Discussion: Patients with proven he- Hepatic Diseases Related to GE patic diseases with autoimmune or viral genesis were ex- • Isolated hypertransaminasemia with parenchymal cluded from the group participating in the current study. damage, reversible with a gluten-free diet (GFD) (celiac The observation and study were conducted on 8 patients hepatitis) [6] – 3 men and 5 women put on a GFD for a period of 6 • Cryptogenic months. All 8 patients were with abnormal hepatic enzyme • Autoimmune hepatic disorders levels. The median levels (±SD) of ASAT and ALAT were • Primary biliary cirrhosis 62.6 ± 16.5 IU/mL with a range of 31-186 IU/mL, and 69.3 • ± 9.3 IU/mL and a range of 63-432 IU/mL, respectively. • Autoimmune cholangitis The median concentrations of alkaline phosphatase were • Primary sclerosing cholangitis ± 280.3±118.7 mmol/L (range -160-428 mmol/L). • Chronic viral infection Six months after GFD, the hepatic enzyme levels • Hemochromatosis decreased to a level of 24.5± 5.1 IU/mL in all patients. • Non-alcoholic [7] Hepatic abnormalities varying from mild changes of he- • Acute patic enzyme levels to liver failure at the time of diagno- • Regenerative nodular hyperplasia sis could be treated with GFD. Its effect on the severity • [8] of other hepatic diseases, for example autoimmune hepa- titis, is not clear yet. Regardless of the effect on the con- PATIENTS AND METHODS comitant hepatic diseases, GFD is needed for the improve- A clinical observation included 112 patients with ment of the symptoms of gluten-sensitive enteropathy and gluten-sensitive enteropathy and 22 patients with gluten all long-term consequences. The lack of sufficient amount sensitivity, who passed through the Clinic of Gastroen- of proof does not undermine the fact that clinicians should terology, Hepatology and Nutrition at St. Marina Univer- consider the diagnosis – gluten-sensitive enteropathy – sity Hospital, Varna for the period from January, 2005 to

2692 https://www.journal-imab-bg.org J of IMAB. 2019 Jul-Sep;25(3) June, 2015. Thirty-four men and 78 women between the The distribution was as follows: Marsh 2 - 1, ages of 18 and 76 were included. The control group con- Marsh3a - 3, Marsh3b - 3, Marsh3c - 1. No IgA deficit sisted of 22 patients of whom 6 were men and 16 – was established in any of the patients. At the start of the women. study only one of the female patients had increased lev- els of total bilirubin, and the rest had normal initial lev- RESULTS AND DISCUSSION els with a mean level of 10.5 ± 0.5 (range 7-30). All patients from the studied group underwent rou- All 8 patients had abnormal hepatic enzyme lev- tine laboratory biochemical testing – AST (normal range els. The mean ASAT and ALAT levels (±SD) were 62.6 ± - 0.0-34 IU/mL), ALT (normal range - 10-35 IU/mL), alka- 16.5IU/mL(range - 31-186IU/mL) and 69.3± 9.3IU/mL line phosphatase (ALP) (normal range - 45-129² U/mL), (range 63-432IU/mL), respectively. The mean alkaline bilirubin - 5.0-21mmol/L. The levels above the upper phosphatase concentration (± SD) was 280.3±118.7mmol/ limit of the range were considered proof of liver failure. L (range -160-428mmol/L). Patients with proven hepatic diseases with autoimmune After a six-month course of GFD, the hepatic en- or viral genesis were excluded from the group in the cur- zyme levels decreased to normal values in all patients - rent study. Monitoring and testing was conducted on 8 24.5±5.1IU/mL and 18-37IU/mL in women (p - 0.04 ); and patients – 3 men and 5 women with altered hepatic func- 28.6± 6 IU/mL and 22-33 IU/mL in men, although no sta- tion. All patients were put on GFD. tistically significant differences were established (p-0.33). Before the start of the study a detailed medical his- The alkaline phosphatase concentration decreased to tory was taken, including past diseases, medicament in- 180.3± 50.6 mmol/L (range 180-280mmol/L), 6 months take, foods with possible toxic effect, and alcohol intake. after GFD. The differences from the pre-GFD levels had An ultrasound study of the hepatobiliary system was con- no statistical significance (p-0.09). The predominant re- ducted. active hepatitis in this cohort – 7%, had complete reso- The mean age of the studied patients was 26.4± 4.8 lution after GFD. years (range 19-32 years). All of them underwent an en- Table 1 presents the serum levels of bilirubin, AST, doscopic study and a morphologic diagnosis was estab- ALT, and ALP, before and after GFD. lished using the Marsh-Oberhuber classification.

Table 1. Results from the hepatic enzyme tests before and after GFD

Total Bilirubin AST (IU/mL) ALT (IU/mL) ALP (mmol/L) Patients Age Gender Before After Before After Before After Before After GFD GFD GFD GFD GFD GFD GFD GFD 1 21 M 8 7 66 24 81 31 243 219 2 19 M 11 9 48 30 76 23 160 148 3 29 M 10 9 31 22 72 27 260 216 4 24 F 7 8 55 21 63 26 328 210 5 33 F 11 9 68 37 108 33 330 220 6 27 F 11 7 55 31 87 30 321 280 7 34 F 30 20 186 31 432 33 428 180 8 30 F 11 10 58 18 73 22 298 186

Several studies report percentages that are a little resolution of the symptoms and biochemical indicators was higher – for example Disky et al. [9] report 15% hyper- observed, starting as early as the third month. transaminasemia among the newly diagnosed patients CONCLUSION with GE. Abdo et al. [10] report 9% hypertransaminasemia. Liver abnormalities varying from hepatic enzyme It is possible that this not-so-striking difference from our level changes to liver failure at the time of GE diagnosis study is due to the fact that the Bulgarian population can be treated with GFD [9]. Its influence of the severity might consume larger quantities of alcohol and have a of the rest of the hepatic diseases, such as autoimmune higher incidence of compared to the other hepatitis, is still not clear. Regardless of its effect on the populations. concomitant hepatic disorders, GFD is necessary for the One of the cases was of particular interest. A young improvement of GE symptoms and all long-term conse- woman presented at the clinic with a severe form of mal- quences [7]. The lack of enough proof does not under- absorption syndrome, acute reactive hepatitis (all possi- mine the fact that clinicians should consider GE as a di- bilities for an underlying hepatic disease were excluded). agnosis in the presence of hypertransaminasemia and a In her case, after timely diagnosis and diet therapy, full lack of other causes of liver failure [11, 12]. We think that

J of IMAB. 2019 Jul-Sep;25(3) https://www.journal-imab-bg.org 2693 the most probable cause of elevated hepatic enzyme lev- order to establish the GE incidence in the different hepatic els is reactive hepatitis presenting with the main disease. [6] diseases and to prove the possible link between them. Despite the accumulation of significant scientific An early diagnosis and GFD therapy might lead to slow- proof in the last decades, future studies are still needed in ing down or stopping the progress of the hepatic disease.

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Please cite this article as: Grudeva L. Gluten-Sensitive Enteropathy – a Potentially Curable Cause of Hepatic Disorders. J of IMAB. 2019 Jul-Sep;25(3):2692-2694. DOI: https://doi.org/10.5272/jimab.2019253.2692

Received: 23/01/2019; Published online: 09/09/2019

Address for correspondence: Lili Grudeva Clinic of Gastroenterology, Hepatology and Nutrition St. Marina University Hospital 1, Hristo Smirnenski Blvd., 9000 Varna, Bulgaria E-mail: [email protected] 2694 https://www.journal-imab-bg.org J of IMAB. 2019 Jul-Sep;25(3)